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Related Concept Videos

RNA Splicing01:32

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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
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Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
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Related Experiment Video

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Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
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Semi-supervised Learning Predicts Approximately One Third of the Alternative Splicing Isoforms as Functional

Yanqi Hao1, Recep Colak1, Joan Teyra2

  • 1Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 1AS, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5S 3G4, Canada.

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|July 7, 2015
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Summary

Alternative splicing significantly impacts protein diversity, with a new algorithm predicting that 32% of exon skipping events yield stable proteins. This finding reveals numerous previously uncharacterized proteins and their functional roles.

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Area of Science:

  • Molecular Biology
  • Genomics
  • Bioinformatics

Background:

  • Alternative splicing is a widespread biological process affecting most human multi-exon genes.
  • The precise impact of alternative splicing on the production of stable, functional proteins remains largely unknown due to experimental limitations and lack of negative data.

Purpose of the Study:

  • To develop and validate a novel computational method for predicting protein-coding alternative splicing events.
  • To estimate the proportion of alternative splicing events that generate stable protein isoforms.
  • To explore the functional and structural implications of alternatively spliced proteins.

Main Methods:

  • Development of a semi-supervised machine learning algorithm named Positive Unlabeled Learning for Splicing Elucidation (PULSE).
  • PULSE utilizes 48 diverse features to analyze splicing events.
  • Algorithm validation using known protein isoforms and mass spectrometry (MS) data, achieving an AU-ROC of 0.85.

Main Results:

  • Prediction that approximately 32% of "exon skipping" alternative splicing events result in stable proteins.
  • Identification of a substantial number of potentially novel protein isoforms arising from alternative splicing.
  • Analysis of the distribution of these protein isoforms across different functional categories and their structural consequences.

Conclusions:

  • Alternative splicing contributes significantly to proteomic diversity, generating a large repertoire of stable, potentially novel proteins.
  • The PULSE algorithm provides a robust tool for investigating alternative splicing and its downstream effects on protein expression.
  • Further research into alternatively spliced proteins is warranted to fully understand their functional significance and structural impact.